NUCLEAR FACTOR-KAPPA-B REPRESSION IN ANTIINFLAMMATION AND IMMUNOSUPPRESSION BY GLUCOCORTICOIDS

The transcription factor nuclear factor-kappa B (NF-kappa B) directs t ranscription of a large number of key molecules in immunological and i nflammatory responses. The recently discovered inhibition of transcrip tional activity of this factor by the activated glucocorticoid recepto r (GR) provides a molecular basis for the potent antiinflammatory and immunosuppressive properties of glucocorticoids. This repressive activ ity of the GR can function independently of transcriptional activity. Because it has been shown that certain steroid receptor ligands can di fferentially address transactivation and transrepression functions, it may be possible to develop ligands that specifically suppress NF-kapp a B activity and as a result, are more efficient in treatment of a var iety of important chronic inflammatory diseases With less severe side effects than those of currently available drugs. (C) 1997, Elsevier Sc ience Inc.